JACC: CARDIOONCOLOGY VOL. 6, NO.

2, 2024

ª 2024 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN

COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER

THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

JACC FAMILY SERIES

Cardiovascular Concerns, Cancer

Treatment, and Biological and
Chronological Aging in Cancer
JACC Family Series

Dina Ioffe, MD,a Sanjana C. Bhatia-Patel, DO,b Sakshi Gandhi, MD,b Eman A. Hamad, MD,b Efrat Dotan, MDa

ABSTRACT

Cardiovascular disease (CVD) and cancer are leading causes of death globally, particularly among the rapidly growing
population of older adults (OAs). CVD is a leading cause of mortality among cancer survivors, often accelerated by
cancer treatments associated with short- or long-term cardiotoxicity. Moreover, there is a dynamic relationship among
CVD, cancer, and aging, characterized by shared risk factors and biological hallmarks, that plays an important role in
caring for OAs, optimizing treatment approaches, and developing preventive strategies. Assessment of geriatric domains
(eg, functional status, comorbidities, cognition, polypharmacy, nutritional status, social support, psychological well-
being) is critical to individualizing treatment of OAs with cancer. The authors discuss considerations in caring for an
aging population with cancer, including methods for the assessment of OAs with CVD and/or cardiovascular risk factors
planned for cancer therapy. Multidisciplinary care is critical in optimizing patient outcomes and maintaining quality of
life in this growing vulnerable population. (J Am Coll Cardiol CardioOnc 2024;6:143–158) © 2024 The Authors. Pub-
lished by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

C ancer and cardiovascular disease (CVD) are

age-related diseases whose increasing preva-
lence parallels the aging population. The
older U.S. population ($65 years of age) grew 5 times
represent 60% of patients with new cancer diagnoses
by 2035, and recent U.S. data predict that 1 in 3 adults
aged $70 years will develop invasive cancer. 3,4 More-
over, the number of cancer survivors has grown as
faster than the general population over the past cen- cancer screening, diagnosis, and treatment improve,
tury, with the fastest growth over the past decade, with 67% of 18 million American cancer survivors
driven by the aging of baby boomers. Older adults aged $65 years in 2022.5 Understanding the interplay
(OAs) represent nearly 17% of the U.S. population between CVD and cancer, 2 major health concerns
and have a life expectancy of 76.4 years.1 CVD inci- affecting OAs and the 2 leading causes of death in
dence and prevalence rise significantly with age, the United States, is vital for developing a holistic
with 80% of CVD-related deaths among treatment approach for OAs with cancer that includes
individuals $65 years of age. 2 OAs are estimated to early intervention and targeted preventive strategies.1

From the aDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; and the bDepartment of
Medicine, Temple University Hospital, Philadelphia, Pennsylvania, USA.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.

Manuscript received October 10, 2023; revised manuscript received February 8, 2024, accepted February 12, 2024.

ISSN 2666-0873 https://doi.org/10.1016/j.jaccao.2024.02.001

144 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

ABBREVIATIONS AGING, CVD, AND CANCER:

AND ACRONYMS HIGHLIGHTS
SHARED RISKS AND BIOLOGY

Cardiovascular disease (CVD) and cancer,
ADL = activities of daily living
CVD risk is closely linked to age-related two major diseases affecting the growing
AE = adverse event
structural and functional changes in the car- number of older adults (OA), have a
CTR-CVT = cancer therapy–
diovascular (CV) system. These changes are bidirectional relationship with shared risk
related cardiovascular toxicity
compounded by risk factors that are more factors and biological hallmarks.
CV = cardiovascular
prevalent with age, such as hypertension
CVD = cardiovascular disease
Care of OA with cancer requires a
(HTN), hyperlipidemia, obesity, and dia-
GA = geriatric assessment comprehensive geriatric assessment
betes.6 Chronic inflammation is a crucial
HER2 = human epidermal (GA), which evaluates several domains
pathophysiological link between CVD and
growth factor receptor 2 that are relevant to management, out-
cancer, contributing to the development and
HF = heart failure comes, and quality of life (QOL) of
progression of atherosclerosis and carcino-
HTN = hypertension patients.
genesis.7 The chronic proinflammatory state
NCCN = National seen with aging, often referred to as
CVD and cardiovascular (CV) risk factors
Comprehensive Cancer Network
“inflammaging,” is associated with increased increase the risk of cancer therapy-
OA = older adult
morbidity and mortality in OAs and has been related cardiovascular toxicity (CTR-CVT)
QOL = quality of life
implicated in many age-related diseases, in OA with cancer, making the overall
including CVD and cancer.7 It likely derives from care of these vulnerable patients more
accumulated cell damage, microbiome by-products, complex.
cellular senescence (terminal cell-cycle arrest), and

Multidisciplinary care that incorporates
immune dysregulation.
the risk of CVD and CTR-CVT in the
Several cellular mechanisms lie at the intersection
overall assessment of OA with cancer is
of aging, cancer, and CVD. Hallmarks of aging
critical to minimizing and preventing
include cellular senescence, altered intracellular
complications, and maintaining QOL.
communication, mitochondrial dysfunction, genomic
instability, epigenetic changes, telomere attrition,
and stem cell exhaustion.8 These hallmarks overlap Aging has long been considered a driver of cancer,
with hallmarks of cancer, particularly the accumu- as evidenced by the increasing incidence of cancer
lation of mutations, cellular damage, decreased im- with age; however, growing data demonstrate a
mune function, and, most important, cellular bidirectional relationship, in which cancer and cancer
senescence.9 Cellular senescence, an irreversible therapies also drive aging and induce cellular senes-
cell-cycle arrest frequently seen in aging tissues, is cence. The recently proposed aging-cancer cycle
provoked when telomeres reach a critically short suggests a dynamic relationship in which aging con-
threshold. Proliferation beyond this limit drives tributes to a “protumorigenic environment,” while
further telomere erosion, ultimately triggering chro- cancer and cancer treatments accelerate aging in
mosomal instability. Short telomere length has been survivors, as evidenced by increased frailty and
implicated in inherited syndromes associated with comorbidities compared with age-matched cancer-
accelerated aging and increased cancer risk, likely as free control subjects.12 Shenoy et al13 described this as
a result of DNA damage, as well as many age-related a “snowball effect,” in which baseline age-related risk
diseases (eg, CVD, diabetes).9 For instance, accu- factors are set in motion by a cancer diagnosis and
mulating senescent cells contribute to vascular gain momentum with direct toxicity of cancer treat-
dysfunction, leading to CV aging and increased risk ment, associated lifestyle changes, and poly-
for CVD.10 Although short telomere length is associ- pharmacy, leading to CVD.
ated with increased cancer risk, many cancers up- Although often viewed as distinct medical condi-
regulate telomerase, an enzyme that counteracts tions, CVD is associated with increased cancer risk,
further telomere shortening, thereby evading cell just as cancer and its treatments increase CVD risk. 14
9
death in the face of critically short telomeres. Considering the increased risk for CVD among OAs
Mitochondrial dysfunction, another hallmark of ag- and the growing number of OAs with cancer, long-
ing, has similarly been implicated in the pathogen- term toxicity of cancer treatments, particularly CV
esis of both CVD and cancer through oxidative stress effects, must be considered. Cancer survivors, many
and accelerated apoptosis or resistance to apoptosis, of whom are older, have an increased risk for CVD
respectively. 10,11 compared with the general population, making CVD
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 145
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

the leading cause of noncancer death among these toxicities, identifying potentially modifiable geri-
patients, often a consequence of cancer therapies.15 atric abnormalities, need for treatment adjustments,
All-cause mortality is significantly worse among and predicting morbidity and mortality. This is
cancer survivors who develop CVD compared to those especially important to OAs, who often value QOL
without CVD (5-year overall survival, 75% vs 87%; 8- over longevity, particularly if treatment-related tox-
year overall survival, 60% vs 81%; P < 0.10).16 These icities carry a risk for functional impairment, cogni-
statistics highlight the critical need to address CV risk tive impairment, or loss of independence.20 Multiple
and cancer therapy-related CV toxicity (CTR-CVT) in domains are affected by aging that affect outcomes
this rapidly growing population. Moreover, OAs often among OAs with cancer and may be missed on routine
face unique challenges when managing CVD and oncologic evaluation: functional status, comorbid-
cancer concurrently. Comorbidities, frailty, and pol- ities, cognition, polypharmacy, nutrition, geriatric
ypharmacy complicate treatment decisions and in- syndromes (eg, falls, frailty, osteoporosis, fatigue),
crease associated toxicities (Central Illustration). social support, and psychological distress21 (Table 1).
Therefore, comprehensive risk assessment and man- FUNCTIONAL STATUS. Functional status, which gener-
agement strategies that address both conditions and ally refers to strength, mobility, and ability to live
associated risk factors are critical. The intersection of independently, is highly variable between aging in-
CVD and cancer in OAs challenges conventional ap- dividuals and is affected by more than chronological
proaches to these conditions as separate entities, age alone. Assessing physical function is critical for
while also offering potential therapeutic targets, cancer treatment decisions, including whether treat-
treatment optimization, and early intervention. ment is appropriate, if dose modifications are neces-
KEY CLINICAL CONSIDERATIONS IN THE sary, and for predicting treatment tolerance.
CARE OF OAs WITH CANCER Although Eastern Cooperative Oncology Group per-
formance status and chronological age are commonly
The care of OAs with cancer is complex and requires a used as surrogates of functional status in determining
holistic approach, particularly when considering po- the most appropriate therapy for an older patient,
tential risks and benefits of cancer treatment. they seldom reflect a patient’s true biological age
Evidence-based and geriatric-specific approaches are given subjectivity and interobserver variability of
necessary for informed decision making and to performance status assessment, as well as significant
improve clinical outcomes, including quality of life heterogeneity in fitness and comorbidities among
(QOL). However, optimal management of OAs with patients of similar age. 22 Self-reported measures of
cancer is limited by a paucity of prospective data functional status can be helpful in assessing fitness
because of the underrepresentation of OAs in clinical and mobility. They consist of activities of daily living
trials. A recent systemic review found that (ADL; basic self-care skills such as bathing, dressing,
patients $70 years of age constituted only 24% of U.S. and feeding) and instrumental ADL (complex skills
Food and Drug Administration clinical trial partici- required for independent living such as shopping,
pants and <10% of National Cancer Institute study medication management, and managing finances).
participants. 17
Moreover, OAs enrolled in these trials The Short Physical Performance Battery and the
are carefully selected and are often healthier and timed up and go test, which assess balance, mobility,
more robust than most OAs with cancer. Age-specific and strength, are predictive of survival, treatment
efficacy and adverse events (AEs) are also under- tolerance, and functional decline.23 The National
reported in phase 3 trials, making it difficult to Comprehensive Cancer Network (NCCN) recommends
extrapolate whether prospective data are generaliz- using an objective measure of physical function and
able to OAs. 18
As a result, oncologists often draw from mobility in addition to self-reported ADL and instru-
clinical experience and clinical trial data from mental ADL when assessing the functional status of
younger cohorts in developing treatment plans for OAs with cancer.24,25
OAs. Notably, emerging data on barriers to clinical COMORBIDITIES. Compared with aged-matched
trial accrual of OAs have served as a launching pad for control subjects, OAs with cancer are more likely to
the significant effort by the National Cancer Institute have multiple comorbidities as they age, including
to promote and enhance accrual of OAs through clin- CVD, HTN, diabetes, chronic kidney disease, arthritis,
ical trial design and use of geriatric assessment (GA). 19 osteoporosis, and cognitive impairment. Comorbid-
A multidimensional evaluation of OAs with cancer ities can represent a competing risk of death for an OA
is critical in understanding overall health, appropri- with cancer and are associated with inferior QOL,
ateness for treatment, risk for treatment-related decreased receipt of anticancer therapy, increased
146 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

C E N TRA L I LL U ST RA TI ON Considerations in Older Adults With Cancer and Cardiovascular

Disease Overlapping

Ioffe D, et al. J Am Coll Cardiol CardioOnc. 2024;6(2):143–158.

(A) Effects of cardiovascular disease (CVD), cancer, and cancer therapy on geriatric domains. Cancer, cancer therapies, and CVD have
overlapping effects on geriatric domains. The intersection of these comorbidities complicates the care of older adults with cancer. Multiple
factors affect the care of older adults with CVD, including age-related, cancer-related, and cardiovascular factors. Geriatric assessment can
identify changes in these geriatric domains and offer potential interventions to improve patient outcomes. (B) Cycle of frailty in older adults
with cancer and CVD. There is dynamic relationship among cancer, cancer therapies, and geriatric domains in older adults with cancer and
CVD, represented here as a cycle of frailty. This highlights the nuanced approach necessary in managing this growing patient population.
CV ¼ cardiovascular disease; DM ¼ diabetes mellitus; HTN ¼ hypertension.
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 147
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

T A B L E 1 Geriatric Domains, Assessment Tools, and Interventions for OAs With Cancer 24

Domain Geriatric Assessment Tools Evaluation Interventions

Functional status ADL: Katz index Dependence with ADL and/or IADL
Prehabilitation
IADL: Lawton-Brody scale Combined score #9
Consider cardiac rehabilitation if comorbid cardio-
Short Physical Performance Time >13 seconds vascular disease and/or risk factors
Battery
Physical and/or occupation therapy
Timed up and go test
Comorbidities Cumulative Illness Rating–Geriatric Comorbid conditions including hearing and/or
Treat and optimize comorbid conditions in coordi-
visual impairment nation with other providers

Screen for potential confounders (eg, depression,
fatigue, nutritional deficiency, endocrine dysfunc-
tion, substance use disorder)
Cognition Mini-Cog Memory loss, confusion, abnormal screening
Assess decision-making capacity
(Mini-Cog score <4, BOMC test score $4)
Further cognitive testing

Close medication reconciliation

Consider neuropsychiatric referral
Polypharmacy Beers criteria Use of $5 prescribed medications
Close medication reconciliation
Medication Appropriateness Index
Review drug interactions and consider deprescribing
at regular intervals

Assess potentially inappropriate medications for OAs
(eg, anticholinergic drugs, long-acting
benzodiazepines)
Nutrition MNA >3-kg unintentional weight loss in 3 mo,
Referral to registered dietician
BMI #21 or $30 kg/m2
Diet and supplement recommendations to prevent
nutritional deficiencies, maintain a healthy weight,
and optimize caloric intake

Consider referrals to speech pathology and/or
occupational therapy if difficulty with swallowing,
eating
Geriatric syndromes Balducci frailty criteria Repeated falls (>3 in 6 mo), severe urinary/
Optimize bone health
Bone health screening fecal incontinence affecting ADL,
Function status assessment
Fall risk assessment osteoporosis
Physical and/or occupation therapy

Home safety evaluation
Social support Assess primary caregiver(s), living Lack of social support, living alone, financial
Review and complete advanced directive
conditions, financial concerns, toxicity
Identify health care proxy and caregiver(s)
transportation needs
Referral to social work and home health services

Home safety evaluation

Screen for elder abuse

Consider counseling
Psychological distress NCCN Distress Thermometer Depression, anxiety, adjustment disorder
More in-depth evaluation if positive screening
Geriatric Depression Scale results

Referral to psychosocial services

Consider chaplain referral per patient beliefs
Geriatric Assessment Tools
Objective Clinical Factors Scores and Recommended Intervention
G8 geriatric screening Determines which patients would Decreased food intake, recent weight loss, Comprehensive geriatric assessment recommended for
tool benefit from a full geriatric mobility, neuropsychological problems (eg, patients with scores #14, which indicates vulnerability
assessment depression, dementia), BMI, polypharmacy
(>3 medications/d), perceived health status
CARG toxicity Graded risk of severe treatment- Age, gastrointestinal or genitourinary cancer, Score 0-5: 30% risk (low)
prediction tool related adverse effects single or multiagent chemotherapy, dose Score 6-9: 52% risk (intermediate)a
attenuation, renal function, hearing Score 10-23: 83% risk (high)b
impairment, falls, assistance with
medication management, mobility, impact
of health on social activity
Chemotherapy Risk Graded risk of hematologic and Hematologic: diastolic blood pressure, IADL, Hematologic score 0 or 1: low risk
Assessment Scale nonhematologic treatment- lactate dehydrogenase, chemotherapy 2 or 3: low to intermediate riska
for High-Age related adverse effects toxicity score 4 or 5: intermediate-high riskb
patients (CRASH) $6: high riskb
Nonhematologic: ECOG performance status, Nonhematologic score 0-2: low risk
Mini-Mental State Examination, MNA, 3 or 4: low to intermediate riska
chemotherapy toxicity score 5 or 6: intermediate to high riskb
$8: high riskb
Combined score 0-3: low risk
4-6: low to intermediate riska
7-9: intermediate to high riskb
$10: high riskb

a
Consider dose modification and/or closer toxicity monitoring. bConsider dose modification with closer toxicity monitoring or best supportive care.
ADL ¼ activities of daily living; BMI ¼ body mass index; BOMC ¼ Blessed Orientation-Memory-Concentration; CARG ¼ Cancer and Aging Research Group Chemotherapy; ECOG ¼ Eastern Cooperative
Oncology Group; IADL ¼ instrumental activities of daily living; MNA ¼ Mini Nutritional Assessment; NCCN ¼ National Comprehensive Cancer Network; OA ¼ older adult.
148 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

treatment-related toxicity, treatment delays or mod- symptoms such as nausea, vomiting, diarrhea, con-
ifications, and higher all-cause mortality. 26-28 stipation, or HTN. Although it may be clinically
Assessing the number and severity of comorbidities appropriate and/or necessary, polypharmacy is asso-
in OAs with cancer as well as their impact on func- ciated with increased drug interactions, treatment-
tional status is essential in formulating and tailoring a related AEs, frailty, and medication nonadherence.31
cancer treatment approach. There are several co- This risk also stems from altered drug metabolism in
morbidity indexes that predict treatment tolerance, OAs due to age-related physiological changes and
risk for treatment discontinuation, and survival, impaired organ function. A comprehensive review of
though most were validated for patients without patient medications, including assessing potentially
cancer, and results vary according to disease type. A inappropriate medications for OAs (eg, anticholin-
recent study showed that the Cumulative Illness ergic drugs, long-acting benzodiazepines), should be
Rating Scale–Geriatric, a weighted index of comor- performed periodically, and deprescribing medica-
bidities by organ system, was most prognostic for 1- tions should be considered.32 Two of the most
29
year mortality among OAs with metastatic cancers. commonly used tools for polypharmacy assessment
The Cumulative Illness Rating Scale–Geriatric, which are the Beers criteria and the Medication Appropri-
can also predict treatment tolerance, is one of the ateness Index, though a validated method to better
most sensitive and commonly used measures of define polypharmacy and appropriate interventions
comorbidities in OAs with cancer.27 in this patient population is needed.33
COGNITION. Cognitive impairment in OAs with can- NUTRITIONAL STATUS. Poor nutritional status and
cer is a risk factor for functional dependence, weight loss are significant risk factors for treatment-
depression, medication nonadherence, and death. 30 related toxicity as well as increased cancer-specific
Dementia, defined by progressive cognitive impair- and overall mortality in OAs.34 Cancer is often
ment involving 1 or more cognitive domains, is more responsible for malnutrition through catabolism and
prevalent in OAs and is a common comorbidity in OAs metabolic dysregulation, leading to anorexia and
with cancer. The NCCN recommends screening for cachexia. Decreased nutritional intake in this setting
cognitive impairment in OAs with cancer using the often compounds underlying age-related sarcopenia
Mini-Cog test, which consists of a clock drawing test (loss of muscle mass) and often translates to
and a 3-word recall, and/or the 6-item Blessed increased frailty. 35 The Mini Nutritional Assessment
Orientation-Memory-Concentration test, which eval- is a validated screening tool that identifies malnutri-
uates orientation, concentration, and memory. 24,25 tion or risk for malnutrition by assessing changes in
Further evaluation is recommended if new cognitive food intake, recent weight loss, mobility, psycholog-
impairment is identified, including screening for po- ical distress, dementia, and body mass index. Appe-
tential confounders such as depression, fatigue, tite stimulants and anticachexia drugs are not
nutritional deficiency, endocrine dysfunction, sub- routinely used in clinical practice because of limited
stance use disorder, and polypharmacy. Importantly, efficacy as well as possible toxicities (eg, thrombo-
cancer treatments such as chemotherapy and brain embolism with megestrol; altered mental status,
radiation can contribute to or precipitate cognitive muscle wasting, and adrenal insufficiency with pro-
decline. Periodic cognition assessment to screen for longed steroid use).36 There are emerging data on the
new or worsening cognitive impairment is recom- use of medical marijuana as an appetite stimulant, as
mended for OAs with cancer who have previously well as an antiemetic and analgesic agent; however,
received cancer treatment or are on active treatment. further research is needed, particularly in OAs whose
Ensuring appropriate social support at home and other geriatric syndromes make this approach risky.37
addressing advanced care planning (eg, advanced Collaboration with a registered dietician and a pa-
directives, designating a health care proxy) are also tient’s social support system or caregiver are impor-
recommended for OAs with identified cognitive tant tools to prevent nutritional deficiencies,
impairment. Targeted interventions such as cognitive maintain a healthy weight, and optimize
rehabilitation have not been studied in OAs with caloric intake.
cancer, particularly among those with baseline GERIATRIC SYNDROMES. Geriatric syndromes are
cognitive impairment. multifactorial clinical conditions that are more
POLYPHARMACY. Polypharmacy, or the use of $5 prevalent with increasing age. They include frailty,
medications, is common in OAs and is closely linked fatigue, osteoporosis, incontinence, delirium, and
to comorbidities. It can result from the addition of falls. Frailty, a syndrome defined by decreased
medications to control cancer treatment–related physiological reserve, is associated with falls,
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 149
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

decreased mobility, dependence with ADL, and and inadequate social support.42 In turn, psycholog-
increased comorbidities. Unlike many other assess- ical distress is associated with decreased QOL,
ment tools that have been developed to evaluate increased symptom burden, increased risk for hospi-
frailty, the Balducci frailty criteria, which are based talization, and inferior survival. 31 The Geriatric
on a comprehensive GA, are specific to OAs with Depression Scale is a tool to screen for depression in
cancer.38 This model defines predictors of frailty as OA without severe cognitive impairment, and trun-
age $85 years, dependence for $1 ADL, $3 comor- cated versions have been validated for screening. The
bidities, and $1 geriatric syndrome. Cancer-related NCCN Distress Thermometer screens for physical,
fatigue is common among patients with cancer, functional, emotional, social, and spiritual concerns
exacerbated by treatment and refractory to rest and and should be paired with a more in depth evaluation
sleep.39 As a result of fatigue, OAs with pre-existing for OA who have positive screening results, as well as
vulnerabilities may experience further declines in referral to psychosocial services. 43
geriatric domains, particularly functional status and In summary, the care of OAs with cancer is com-
independence. Osteoporosis is another major issue plex and nuanced, as these geriatric domains are
for OAs with cancer, particularly with a concurrent intertwined: a change in one often has a ripple effect
risk for falls and with cancer treatments that promote on other aspects of geriatric health (Central
loss of bone density and muscle mass (eg, hormonal Illustration). Cancer and cancer treatments can affect
therapies, steroids). Optimizing bone health through all of these domains, leading to increased frailty, poor
appropriate screening, vitamin D supplementation, treatment tolerance, and inferior outcomes. For
and bone-modifying agents as indicated is essential example, neuropathy or cognitive impairment from
in the care of OAs with cancer and cancer survivors. cancer treatment can lead to increased risk for falls in
This is particularly important considering that falls an already vulnerable OA, which cascades to potential
are another major health concern for OAs and are fractures, decreased mobility and functional status,
more common in OAs with cancer than cancer-free loss of independence, and inability to receive further
OAs. Fall risk can increase because of cancer, treatment because of worsening frailty. Similarly,
treatment-related fatigue, sarcopenia, peripheral treatment that can cause CV toxicity (eg, heart failure
neuropathy caused by therapy, and weakness.31 The [HF], HTN, thromboembolism, arrhythmias, hypo-
timed up and go test or measuring gait speed are tension) can complicate treatment approaches and
simple tools to assess balance and fall risk. 40 Mini- outcomes in OAs with cancer who have or are at high
mizing risk of falls by promoting exercise, optimizing risk for comorbid CVD. These complications may lead
home safety, minimizing polypharmacy, and dis- to increased frailty, hospitalization, increased poly-
continuing sedating or psychotropic medications, is a pharmacy, and often cancer treatment discontinua-
critical aspect of comprehensive geriatric care. tion or delay. Alternatively, concerns for specific
treatment-related toxicity or limited functional
SOCIAL SUPPORT. Reliable social support is also
reserve in OAs with cancer and multiple comorbid-
fundamental to optimizing treatment outcomes in
ities complicate treatment decisions and often
OAs with cancer. Reviewing a patient’s living condi-
necessitate treatment modification. For example,
tions, financial status, transportation options, and
comorbid diabetes-related peripheral neuropathy
potential caregivers will help identify and preempt
may preclude some OAs from chemotherapies that
potential barriers to effective care. Advanced care
can worsen neuropathy (eg, oxaliplatin for gastroin-
planning, referrals to social work, and obtaining
testinal malignancies and taxanes for breast cancer)
home health assistance are critical in facilitating
despite their proven efficacy in those diseases.
treatment plans and optimizing patient outcomes.
The NCCN OA Oncology Panel also recommends a PERSONALIZING CARE OF OAs USING GA
social work referral to evaluate these aspects of social
support, as well as to assess home safety and screen Given the relationship between these geriatric do-
for elder abuse.24 mains to cancer care and oncologic treatment de-
PSYCHOLOGICAL DISTRESS. Psychological distress, cisions, considering vulnerabilities revealed through
including depression, anxiety, and adjustment dis- comprehensive GA often influences treatment rec-
order, is reported in approximately 40% OAs with ommendations and goals of care. Weighing the risks
cancer.41 A prospective study of OAs with recently and benefits of cancer treatments in this patient
diagnosed cancer showed that depression was inde- population is challenging, as treatment-related com-
pendently associated with impaired functional status, plications can be more severe because of age- and
cognitive impairment, comorbidities, polypharmacy, disease-related physiological changes, leading to
150 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

worsening comorbidities, functional status, QOL, and and treatment-specific tools to maximize the predic-
survival. GA can further inform shared decision tive value of GA. The Cancer and Aging Research
making by assessing appropriateness for treatment, Group Chemotherapy Breast Cancer score, the only
predicting treatment-related toxicities, and identi- validated disease-specific GA tool thus far, predicts
fying modifiable geriatric factors that improve treat- the risk for chemotherapy-related AEs in OAs with
ment outcomes (Table 1). early-stage breast cancer.55 Similarly, geriatric tools
Several studies have demonstrated that GA-based and biomarkers to predict CTR-CVT are not available
interventions and cancer care decrease functional at this time. Ezaz et al56 developed a proof-of-concept
44-46
decline, hospitalizations, and mortality. Howev- 7-factor risk score on the basis of Surveillance,
er, time and personnel constraints remain barriers to Epidemiology, and End Results–Medicare claims data
the widespread adoption of GA-guided cancer care.47 to determine the 3-year risk for cardiomyopathy and
GA screening tools and chemotherapy toxicity pre- HF after adjuvant trastuzumab (an anti–human
diction calculators offer faster, simplified evaluations epidermal growth factor receptor 2 [HER2] mono-
of OAs with cancer. The G8 geriatric screening tool clonal antibody), which requires further validation.
identifies OAs with cancer who would benefit from a GA also leads to nononcologic interventions aimed
comprehensive GA, which remains the gold standard at addressing vulnerabilities, including poly-
for a complete evaluation of this patient population pharmacy, nutritional support, optimizing comor-
(Table 1).48 The Chemotherapy Risk Assessment Scale bidities, and social interventions. A systemic review
for High-Age Patients (CRASH) and Cancer and Aging of 61 geriatric oncology studies revealed that having a
Research Group Chemotherapy (CARG) toxicity tool prespecified intervention protocol led to non-
are validated to predict the risk for treatment-related oncologic interventions in more than 70% of patients,
toxicity in OAs with cancer.22,49 compared with 26% in studies that did not. 46
GA influences treatment decisions for OAs with Addressing identified vulnerabilities in cognitive
cancer, including changing, intensifying, reducing, or impairment, polypharmacy, mobility, and social
delaying therapy in up to 82% of patients, leading to support were at least 5 times less likely without a
fewer serious AEs.50 Chemotherapy deintensification prespecified intervention. GA is also associated with
is most common, representing a median 73% of increased advanced care planning and goals of care
treatment changes in a recent systemic review. 46 GA- discussions, as well as improved QOL and physical
driven interventions are associated with a high rate of functioning. 46,57 Additionally, GA and GA-guided
planned chemotherapy completion, fewer treatment recommendations improved both patient and care-
modifications, and decreased toxicity. 51 The GAIN giver satisfaction and increased discussion of age-
(Geriatric Assessment-Driven Intervention) and related concerns in vulnerable OAs with cancer in
GAP70þ (A Geriatric Assessment Intervention for Pa- the prospective COACH (Improving Communication
tients Aged 70 and Over Receiving Chemotherapy or in Older Cancer Patients and Their Caregivers)
Similar Agents for Advanced Cancer: Reducing study.58 These data highlight the importance of using
Toxicity in Older Adults) trials validated the benefit of GA and GA screening tools in conjunction with pre-
GA-guided oncologic care, demonstrating improved specified interventions to optimize treatment ap-
treatment tolerance with a 10% to 20% decrease in proaches, provide holistic care, and improve patient
severe AEs.52,53 GA-guided care is recommended by outcomes in OAs with cancer.
the NCCN and the American Society of Clinical
Oncology in managing OAs with cancer as it identifies RECOMMENDATIONS FOR MANAGING OAs
geriatric vulnerabilities, provides prognostic infor- WITH COMORBID CV RISK
mation, and is critical in individualizing and opti-
mizing treatment. 24,54 Frailty and CVD are closely related, as the prevalence
However, the Chemotherapy Risk Assessment Scale of both increases with age.59 As such, managing the
for High-Age Patients and Cancer and Aging Research interaction among CVD, geriatric syndromes, and
Group Chemotherapy tools predict chemotherapy potentially cardiotoxic cancer therapies necessitates
tolerance but do not account for specific disease and clearer geriatric cardiology and oncology approaches
treatment variables as they were validated in a to minimize CV risk in this vulnerable, heterogeneous
heterogenous population of OAs with cancer. The patient population. Involving a geriatrician in the
treatment landscape in oncology has dramatically management of these patients can offer additional
changed with novel therapies since these tools were support in managing the complex care of OAs with
developed and validated, limiting their broad appli- cancer. Improving screening, prevention, and man-
cability and highlighting the need for more disease- agement of CVD in OAs with cancer should aim to
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 151
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

minimize CV complications that can worsen frailty We support the use of the Heart Failure
and other geriatric domains, decrease cancer treat- Association–International Cardio-Oncology Society
ment tolerance, and increase mortality. pretreatment CV risk assessment tool, which in-
Although CV toxicities can arise across many corporates age, comorbidities, lifestyle risk factors
different oncologic drug classes and affect patients (eg, smoking, alcohol use, obesity), prior cardiotoxic
across the age spectrum, there are some key consid- cancer treatment, cardiac biomarkers, lipid panel,
erations when planning such therapies for OAs electrocardiography, and echocardiography. 63 High-
(Table 2). Cardiotoxicity prevention strategies in OAs risk or very high-risk patients require cardiology
with cancer require CVD risk assessment, careful referral and a multidisciplinary discussion of the
consideration of cumulative CTR-CVT risk, a plan for risk/benefit ratios of potentially cardiotoxic cancer
CTR-CVT monitoring, and patient education. Ideally, treatments. Moderate risk should prompt closer
this should be done collaboratively between the oncology follow-up, while routine follow-up is
oncologist and cardiologist, who develop a plan on appropriate for patients at low risk. Similarly, the
the basis of cancer treatment options (ie, cardiotox- European Society for Medical Oncology cardio-
icity risk), underlying CVD, CV risk factors, and a oncology guidelines recommend consideration of
baseline CV assessment. Risk factors for CTR-CVT are alternative noncardiotoxic cancer treatments for
variable and often associated with increased cumu- patients with left ventricular ejection
lative dose (eg, anthracyclines), concurrent poten- fractions #40% to 50%, as well as for those with left
tially cardiotoxic systemic therapies, combination of ventricular ejection fractions <40% in addition to
systemic and radiation therapy, radiation therapy cardioprotective therapy. 60 Periodic assessment of
field, age of exposure, baseline CVD or CV risk factors left ventricular ejection fraction and cardiac bio-
(eg, reduced ejection fraction with anti-HER2 mono- markers is recommended, though the duration and
clonal antibodies or HTN with tyrosine kinase or frequency of monitoring depend on specific cancer
vascular endothelial growth factor inhibitors). We treatment and baseline CV risk.
recognize the need for greater data in OAs, specif- Primary prevention consists of optimizing baseline
ically with respect to CV screening, assessment, pre- CVD or CV risk factors and potentially car-
vention, and survivorship. In the following dioprotective medications. It should be considered in
discussion, we describe the current state of knowl- OAs who are receiving therapies with high cardiotoxic
edge as it pertains to the general population in cardio- potential or those with pre-existing CVD, as they are
oncology and how it might apply to OAs. at greater risk for CTR-CVT. Primary prevention with
CV SCREENING, ASSESSMENT, AND PREVENTION. Screening cardiac medications (eg, angiotensin-converting
and assessment of CV risk should focus on coronary enzyme inhibitors, angiotensin receptor blockers,
artery disease, HTN, and HF, as these are the most statins) have not consistently shown prevention of
common long-term sequelae of cardiotoxic cancer CTR-CVT and are not routinely recommended in the
therapies. Furthermore, comorbid cardiac conditions absence of other indications. 60 Similarly, primary and
and modifiable risk factors, including HTN, hyper- secondary prevention of anthracycline-induced car-
lipidemia, diabetes, obesity, and smoking, should be diomyopathy using angiotensin-converting enzyme
treated and optimized per respective guidelines in inhibitors and angiotensin receptor blockers has
OAs at risk for CTR-CVT. 60 Measuring serum cardiac yielded mixed results.64 Lisinopril or carvedilol use
biomarkers (ie, troponin and natriuretic peptide) during treatment with trastuzumab (anti-HER2 ther-
before treatment can help identify patients at higher apy) and anthracycline as primary prevention was
risk for CTR-CVT and the development or progression effective in minimizing treatment interruptions in
of CVD, as well as those who might benefit from pri- trastuzumab therapy; however, there was no differ-
mary cardiotoxicity prevention or closer monitoring ence in CTR-CVT.65 The prospective SAFE-HEaRT
61
on treatment. Several alternative biomarkers have (Cardiac Safety Study in Patients With HER2þ Breast
been proposed, though none have been validated in Cancer) trial offers a potential preventive surveillance
larger patient populations or in OAs. Serum bio- approach in patients with borderline asymptomatic
markers should be paired and interpreted with car- left ventricular ejection fraction to receive HER2-
diac imaging, primarily echocardiography to assess directed therapies who may have otherwise been
left ventricular ejection fraction. 62 Baseline electro- precluded from these drugs. 66 Medication-based
cardiography and a lipid panel are also recommended prevention in patients undergoing pretreatment
in patients with CVD, those with CV risk factors, evaluation for potentially cardiotoxic therapies
and/or those being considered for potentially car- should be evaluated in a multidisciplinary setting
diotoxic therapy (Figure 1). with oncology and cardiology. 63
152 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

T A B L E 2 Cancer Treatments and Associated CV Concerns for OAs

Recommendations for
Associated Modifications and Specific Recommendations
Treatment General Indication(s) CV Toxicity Risk in OAs Monitoring for OAs

Anthracyclines
Doxorubicin, Multiple cancers: acute Acute CM (<5%) Risk for HF increases Two-dimensional Pegylated liposomal
daunorubicin, lymphoblastic leukemia, Arrhythmias, with time and age echocardiography within 1 y of doxorubicin has a safer
75
idarubicin bladder, breast, pericarditis, (w5%) completing anthracycline cardiac toxicity profile and
lymphomas myocarditis, and/or therapy (high cumulative dose does not affect cancer
acute HF or a low cumulative dose treatment efficacy76,77
69
Chronic CM (#5%) þ $1 risk factor for HF)
Dose dependent
Dilated CM, HF,
arrhythmias
Fluoropyrimidines
5-FU GI malignancies, advanced Coronary vasospasm, Cardiotoxicity is rare Screen for CVD and GA-based dose modification and
head and neck cancers chest pain, and does not CV risk factors interventions to assist with
Capecitabine (oral GI and metastatic breast palpitations (<5%) increase based on patient selection and increase
prodrug of 5-FU) cancers; radiosensitizer MI and cardiac arrest age alone79,80 number of patients
with radiation therapy rare (<2%)78 completing planned
treatment without worsening
toxcitiy81,82
Anti-HER2 therapies
Trastuzumab HER2-positive breast, Decreased LVEF Risk for cardiotoxicity Consider primary prevention with Use GA to determine fitness for
colorectal, GEJ, gastric (2%-5%), severe is similar in OAs lisinopril or carvedilol during therapy
cancers cardiotoxicity and is treatment with trastuzumab þ Optimize borderline LVEF and
(#1%)83 proportional to anthracycline65 careful consideration of CV
treatment Has been shown to decreased risk factors
duration treatment interruptions with Use with caution in OAs who
trastuzumab alone but not have previously received
affect cardiotoxicity rates anthracyclines
Baseline echocardiography and
monitoring every 12 wk during
treatment, followed by
echocardiography every 3 mo
for at least 2 y after
completing HER2 therapy70
Pertuzumab HER2-positive breast in No increased toxicity No increased Screen for CVD and Use with caution given
combination with compared with cardiotoxicity CV risk factors increased risk for diarrhea
trastuzumab trastuzumab compared with and fatigue in OAs85
alone84 trastuzumab
alone
Trastuzumab HER2-positive metastatic Decreased LVEF No increased Screen for CVD and Use with caution given
emtansine breast cancer (#2%)86 cardiotoxicity on CV risk factors increased risk for nausea,
the basis of age diarrhea, skin changes, and
fatigue in OAs86
Trastuzumab HER2-positive breast, GEJ, Decreased LVEF Age-specific Use with caution if underlying lung NA
deruxtecan gastric cancers (2%-5%), severe cardiotoxicity disease
LV dysfunction data unavailable
(0.5%)87,88
Targeted therapies
VEGF inhibitors Multiple cancers: cervical, HTN most common; No increased Close blood pressure monitoring Close blood pressure monitoring
(bevacizumab, colorectal, glioblastoma, arterial/venous cardiotoxicity on and management during and management before and
ramucirumab) hepatocellular, non–small thromboembolism the basis of therapy during therapy
cell lung, ovarian, renal and CM rare89 age90,91
cell
Tyrosine kinase Multiple cancers: chronic HTN, arrhythmias, No increased Blood pressure monitoring, Close blood pressure monitoring
inhibitors lymphocytic leukemia, arterial/venous cardiotoxicity periodic electrocardiogram and management before and
chronic myeloid leukemia, thromboembolism, based on age based on drug toxicity profile during therapy
hepatocellular, prostate, bleeding (rates (age-specific data
renal cell variable on the are limited)
basis of drug, dose,
and disease)
Continued on the next page

SURVIVORSHIP RECOMMENDATIONS. Cancer survi- pretreatment CV risk assessment) undergo CV

vors should be regularly assessed and screened for assessment every 3 months for the first year after
emerging CVD (eg, blood pressure monitoring, dia- treatment and then annually; low- and moderate-risk
betes screening, atherosclerotic CVD risk score). The patients should undergo annual assessment post-
European Society of Cardiology recommends that treatment. 63 Survivors at high risk for developing
high-risk or very high-risk patients (on the basis of CVD on the basis of treatment or disease should also
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 153
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

T A B L E 2 Continued

Recommendations for
Associated Modifications and Specific Recommendations
Treatment General Indication(s) CV Toxicity Risk in OAs Monitoring for OAs

Endocrine therapies
Androgen deprivation Prostate cancer HTN, rarely atrial No increased Screen for CVD and CV risk factors; Consider alternatives to
therapy: fibrillation, CAD, cardiotoxicity on blood pressure monitoring abiraterone, that require
abiraterone, acute coronary the basis of age concomitant steroid use92,93
darolutamide, syndrome92-94 (age-specific data Close monitoring for
apalutamide, are limited) osteoporosis
enzalutamide
Aromatase inhibitors Hormone receptor–positive HF, venous No increased Screen for CVD and Close monitoring for
(eg, anastrozole) breast cancer thromboembolism, cardiotoxicity on CV risk factors osteoporosis
MI rare (<2%)95 the basis of age
Other therapies
Immune checkpoint Multiple cancers: colorectal, Myocarditis, No increased Consider other IO-related Use high-dose steroids with
inhibitors hepatocellular, melanoma, arrhythmias; rarely cardiotoxicity on toxicities if CV IO toxicity caution when treating IO-
non–small cell lung, renal CM, HF, pericardial the basis of age suspected related toxicity
cell disease (age-specific data
are limited)
Chimeric antigen Lymphoma, multiple myeloma Reduced LVEF, Limited data in OAs Cardiac evaluation and Cardiac evaluation and
receptor T-cell arrhythmias, with mixed optimization in all patients optimization and GA-guided
therapy cardiogenic shock, results on risk for care
cardiac arrest cardiotoxicity in
OAs compared
with younger
patients
RT Multiple cancers CAD, pericardial Risk for cardiotoxicity Modification and toxicity Avoid adjuvant RT for OAs with
disease, aortic increases with management depend on dose breast cancer $70 years of
regurgitation, time from RT and and radiation field; consider age97
96
aortic stenosis, increasing age intensity-modulated RT to
nonischemic CM limit toxicity to surrounding
tissue or stereotactic body
radiation therapy in the
palliative setting for shorter,
more convenient treatment if
medically appropriate

5-FU ¼ fluorouracil; CAD ¼ coronary artery disease; HF ¼ heart failure; CM ¼ cardiomyopathy; CV ¼ cardiovascular; CVD ¼ cardiovascular disease; GA ¼ geriatric assessment; GEJ ¼ gastroesophageal
junction; GI ¼ gastrointestinal; HER2 ¼ human epidermal growth factor receptor 2; HF ¼ heart failure; HTN ¼ hypertension; IO ¼ immunotherapy; LV ¼ left ventricular; LVEF ¼ left ventricular ejection
fraction; NA ¼ not applicable; OA ¼ older adults; RT ¼ radiation therapy; VEGF ¼ vascular endothelial growth factor.

be referred to cardiology for comanagement and HF complexity of pretreatment CV risk assessment in

screening. 67 Aspirin use for secondary prevention and OAs with cancer. As such, GA in this patient popula-
potentially primary prevention may be considered tion is critical in addition to the CV risk assessment
per recommendations from the U.S. Preventive Ser- outlined earlier. Most GA screening tools overlap with
vices Task Force.68 geriatric cardiology screening tools and are recom-
The NCCN survivorship guidelines recommend mended in this patient population, including
considering echocardiography within 1 year of ADL and instrumental ADL assessment, the Short
completing anthracycline-based therapy or in pa- Physical Performance Battery, the timed up and go
tients who have $1 risk factor for HF.69 Baseline test, the Cumulative Illness Rating Scale–Geriatric,
echocardiography and monitoring every 12 weeks the Mini-Cog, the Mini Nutritional Assessment, and
during treatment are recommended with most HER2 the Geriatric Depression Scale.71
therapies, followed by echocardiography every Assessing polypharmacy, which is associated with
3 months for at least 2 years after completing HER2 frailty, is particularly important in OAs with comorbid
therapy70 (Table 2). Imaging in patients who receive cancer and CVD or CV risk factors. Guideline-directed
other potentially cardiotoxic therapies should be medical therapy for CVD includes several medica-
based on individual risk. tions, which in addition to those added as supportive
care for cancer treatment may increase the risk for
THE INTERSECTION OF GERIATRIC adverse drug reactions and interactions. Adverse
CARDIOLOGY AND GERIATRIC ONCOLOGY drug reactions are common causes of emergency
department visits or hospitalizations in OAs in the
Comorbidities, polypharmacy, and age-related func- United States, with 42% of emergency department
tional and cognitive impairment compound the visits resulting in hospitalization because of CV drugs
154 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

F I G U R E 1 Assessment and Management of Older Adults With Cancer

ASSESSMENT OF RISK FACTORS

Age ≥ 65 years, Hypertension, Hyperlipidemia, Diabetes, Obesity, Alcohol/Tobacco Use,
Prior Exposure to Cardiotoxic Systemic Therapy, Prior Thoracic Radiation

RISK REDUCTION GERIATRIC ASESSMENT BIOMARKER ASSESSMENT CARDIAC TESTING NUTRITIONAL ASSESSMENT FUNCTIONAL ASSESSMENT

Mini Nutritional Assessment Geriatric Assessment Tools

HTN goal ≤ 130/80 mmHg Age ≥ 65 years
Complete metabolic panel (MNA) (Short Physical Performance
Diabetes HbA1c < 6.5% Comorbidities
Complete blood count Transthoracic Battery Test, Timed Up and
HLD Initiate statin therapy if Polypharmacy
High sensitivity troponin echocardiogram (TTE) Obtain at baseline & Go Test)
ASCVD > 7.5% Functional assessment
NT-ProBNP measure at regular intervals
Lifestyle modifications diet, Psychosocial status
Hemoglobin A1c Electrocardiogram (ECG) to monitor nutritional status 6-minute Walk Test
exercise Cognition
Lipid panel in addition to weight loss
Smoking cessation Nutrition
monitoring

G8 Screening CRASH &

Tool CARG Toxicity Cardiopulmonary exercise
ECG
Assess frailty & Tools TTE testing
QTc monitoring
need for Assess risk of Assess LVEF Cardiac rehabilitation
Screen for
comprehensive chemotherapy- Screen for PAH Establish baseline & optimize
arrhythmias
geriatric related toxicity functional status accordingly
assessment

Routine
monitoring
during and after
therapy with
anthracyclines
& anti-HER2
therapies

This algorithm summarizes the authors’ recommendations for assessing and managing the care of older adults with cardiovascular disease or risk factors prior to or
following cancer treatment. This approach helps identify patients at risk for treatment-related cardiotoxicity and those who may need optimization of cardiovascular
factors to prevent other treatment-related adverse effects. ASCVD ¼ atherosclerotic cardiovascular disease risk score; CAD ¼ coronary artery disease; CARG ¼ Cancer
and Aging Research Group Chemotherapy; CRASH ¼ Chemotherapy Risk Assessment Scale for High-Age Patients; HbA1c ¼ glycated hemoglobin; HER2 ¼ human
epidermal growth factor receptor 2; HLD ¼ hyperlipidemia; HTN ¼ hypertension; LVEF ¼ left ventricular ejection fraction; NT-ProBNP ¼ N-terminal pro–brain type
natriuretic peptide; PAH ¼ pulmonary arterial hypertension; QTc ¼ corrected QT interval.

(eg, angiotensin-converting enzyme inhibitors, during cancer treatment to optimize blood pressure,
angiotensin receptor blockers, diuretic agents, anti- bleeding risk, and/or volume status. The risk for
arrhythmic medications) and 51% related to cancer medication-induced hypoglycemia, which can lead to
therapies. 72 Risk for hospitalization for adverse drug falls, syncope, and hospitalization (emergency
reactions increases with age and with polypharmacy department visits or hospitalization related to insu-
($5 medications). Polypharmacy is also very common lin, 13.9%; oral hypoglycemic agents, 10.7%), is also
among patients with HF, especially OAs. More than an important consideration in OAs with cancer, who
55% of patients $75 years of age with HF were may have oscillating glycemic control needs in the
taking $10 medications, approximately 20% of whom setting of poor appetite and altered metabolism due
had comorbid geriatric conditions and about 15% of to malignancy. 72 Close medication reconciliation, re-
73
whom had cancer. Even more OAs (84%) were tak- view of drug interactions, and considering depres-
ing at least 5 medications, which increased to 95% cribing at regular intervals is critical in preventing
after admission for HF.73 Notably, most medications functional decline, AEs, and worsening frailty in this
were for non-CV indications. Another study failed to vulnerable population.
demonstrate improved frailty scores with decreasing Functional status, mobility, and strength are also
antihypertensive medications in OAs $80 years of important in assessing OAs with cancer and CVD.
age, suggesting that focusing on noncardiac medica- Falls are higher in adults with CVD, a risk com-
tions may be more beneficial in this population when pounded by aging-related physiological changes (eg,
optimizing polypharmacy.74 Although there are no sensory impairment, cognitive impairment, reduced
clear guidelines for the a priori adjustment of cardiac autonomic reflexes, impaired volume homeostasis)
medications, patients may require drug modifications and polypharmacy. 71 Assessing functional status and
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 155
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

screening for falls can be important, and simple tools outcomes, including advanced care planning,
in preventing progressive frailty and AEs during communication, age-related issues, patient satisfac-
cancer treatment. Additionally, some evidence in OAs tion, and QOL. Further research to identify risk fac-
without cancer suggests that cardiac rehabilitation tors and novel management approaches of CVD in
may prevent or reverse frailty, as well as improve patients with cancer and survivors is warranted, with
functional status as measured by the timed up and go a particular focus on OAs, who account for most pa-
test and the Short Physical Performance Battery.59 tients facing this significant challenge.
Interval assessment of these domains during and Another essential aspect of care of this population
after cancer treatment, particularly functional sta- is shared decision making involving oncology, cardi-
tus and polypharmacy, in addition to serial ology, and potentially geriatrics to discuss treatment
biomarker and imaging, may offer valuable infor- choices that maintain good QOL, functional status,
mation before CTR-CVT or treatment-related and independence. This is particularly important
decline in geriatric domains become clinically when considering competing risks of death and
apparent or significant. treatment trade-offs (eg, cancer treatment can
potentially prolong life at the expense of worsening
CONCLUSIONS
CVD). Revisiting questions regarding “what matters”
is equally important as interval GA, considering pa-
Caring for OAs with cancer requires carefully
tient goals and priorities may change over time. This
balancing the risks and benefits of cancer therapy,
holistic, patient-centered multidisciplinary care ad-
comorbidities, associated toxicities, and other geri-
dresses the complexity of managing these patients as
atric factors. As the number of OAs with cancer un-
we await prospective data to further hone our treat-
dergoing therapy and older survivors continues to
ment approach.
rise, we expect to see a parallel increase in CVD
incidence related to cancer treatments and underly-
FUNDING SUPPORT AND AUTHOR DISCLOSURES
ing aging processes. The use of GA combined with
thorough evaluation and optimization of CV risk fac- The authors have reported that they have no relationships relevant to
tors before and after the completion of cancer treat- the contents of this paper to disclose.

ment is critical in tailoring therapy. This personalized

approach in a heterogenous population can limit ADDRESS FOR CORRESPONDENCE: Dr Efrat Dotan,
treatment-related toxicity while improving the like- Department of Medical Oncology, Fox Chase Cancer
lihood of treatment completion. Moreover, GA and Center, 333 Cottman Avenue, Philadelphia, Pennsyl-
GA-guided interventions improve nononcologic vania 19111, USA. E-mail: efrat.dotan@fccc.edu.

REFERENCES

1. Xu JQMS, Kochanek KD, Arias E. Mortality in the of the week. J Am Coll Cardiol. 2019;74(6):804–813. 12. Sedrak Mina S, Cohen HJ. The aging–cancer
United States, 2021. NCHS Data Brief No. 456. https://doi.org/10.1016/j.jacc.2019.06.053 cycle: mechanisms and opportunities for interven-
Hyattsville, MD: National Center for Health Sta- tion. J Gerontol A Biol Sci Med Sci. 2022;78(7):1234–
7. Franceschi C, Garagnani P, Parini P, et al.
tistics; 2022. 1238. https://doi.org/10.1093/gerona/glac247
Inflammaging: a new immune-metabolic viewpoint
2. Benjamin EJ, Muntner P, Alonso A, et al. Heart for age-related diseases. Nat Rev Endocrinol. 13. Shenoy C, Klem I, Crowley AL, et al. Cardiovas-
disease and stroke statistics—2019 update: a 2018;14(10):576–590. https://doi.org/10.1038/ cular complications of breast cancer therapy in older
report from the American Heart Association. Cir- s41574-018-0059-4 adults. Oncologist. 2011;16(8):1138–1143. https://
culation. 2019;139(10):e56–e528. https://doi.org/
doi.org/10.1634/theoncologist.2010-0348
10.1161/CIR.0000000000000659 8. López-Otín C, Blasco MA, Partridge L, et al. The
3. Pilleron S, Sarfati D, Janssen-Heijnen M, hallmarks of aging. Cell. 2013;153(6):1194–1217. 14. Bell CF, Lei X, Haas A, et al. Risk of cancer after
et al. Global cancer incidence in older adults, https://doi.org/10.1016/j.cell.2013.05.039 diagnosis of cardiovascular disease. J Am Coll
2012 and 2035: a population-based study. Int J Cardiol CardioOnc. 2023;5(4):431–440. https://
9. Aunan JR, Cho WC, Søreide K. The biology of
Cancer. 2019;144(1):49–58. https://doi.org/10. doi.org/10.1016/j.jaccao.2023.01.010
aging and cancer: a brief overview of shared and
1002/ijc.31664
divergent molecular hallmarks. Aging Dis. 2017;8(5): 15. Sturgeon KM, Deng L, Bluethmann SM, et al.
4. Siegel RL, Miller KD, Wagle N. Cancer statistics, 628. https://doi.org/10.14336/ad.2017.0103 A population-based study of cardiovascular dis-
2023. CA Cancer J Clin. 2023;73(1):17–48. https:// ease mortality risk in US cancer patients. Eur Heart
doi.org/10.3322/caac.21763 10. Abdellatif M, Rainer PP, et al. Hallmarks of J. 2019;40(48):3889–3897. https://doi.org/10.
cardiovascular ageing. Nat Rev Cardiol. 1093/eurheartj/ehz766
5. Miller KD, Nogueira L, Devasia T, et al. Cancer
2023;20(11):754–777. https://doi.org/10.1038/
treatment and survivorship statistics, 2022. CA 16. Armenian SH, Xu L, Ky B, et al. Cardiovascular
s41569-023-00881-3
Cancer J Clin. 2022;72(5):409–436. https://doi. disease among survivors of adult-onset cancer: a
org/10.3322/caac.21731 11. Luo Y, Ma J, Lu W. The Significance of mitochon- community-based retrospective cohort study.
6. Triposkiadis F, Xanthopoulos A, Butler J. Cardio- drial dysfunction in cancer. Int J Mol Sci. 2020;21(16): J Clin Oncol. 2016;34(10):1122–1130. https://doi.
vascular aging and heart failure: JACC review topic 5598. https://doi.org/10.3390/ijms21165598 org/10.1200/JCO.2015.64.0409
156 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

17. Sedrak MS, Freedman RA, Cohen HJ, et al. with cancer: assessment, management, and mood disorders. J Clin Oncol. 2007;25(29):4670–
Older adult participation in cancer clinical trials: a research opportunities. J Clin Oncol. 2021;39(19): 4681. https://doi.org/10.1200/JCO.2006.10.0438
systematic review of barriers and interventions. CA 2138–2149. https://doi.org/10.1200/jco.21.00239
44. Ellis G, Gardner M, Tsiachristas A, et al.
Cancer J Clin. 2021;71(1):78–92. https://doi.org/
31. Magnuson A, Sattar S, Nightingale G, Saracino R, Comprehensive geriatric assessment for older
10.3322/caac.21638
Skonecki E, Trevino KM. A practical guide to geriatric adults admitted to hospital. Cochrane Database
18. BrintzenhofeSzoc K, Krok-Schoen JL, Canin B, syndromes in older adults with cancer: a focus on Syst Rev. 2017;9:CD006211. https://doi.org/10.
et al. The underreporting of phase III chemo- falls, cognition, polypharmacy, and depression. Am 1002/14651858.CD006211.pub3
therapeutic clinical trial data of older patients Soc Clin Oncol Educ Book. 2019;39:e96–e109.
45. Mohile SG, Velarde C, Hurria A, et al. Geriatric
with cancer: a systematic review. J Geriatr Oncol. https://doi.org/10.1200/edbk_237641
assessment–guided care processes for older
2020;11(3):369–379. https://doi.org/10.1016/j.
32. Sharma M, Loh KP, Nightingale G, Mohile SG, adults: a Delphi consensus of geriatric oncology
jgo.2019.12.007
Holmes HM. Polypharmacy and potentially inap- experts. J Natl Compr Canc Netw. 2015;13(9):1120–
19. Le-Rademacher J, Mohile S, Unger J, et al. Trial propriate medication use in geriatric oncology. 1130. https://doi.org/10.6004/jnccn.2015.0137
design considerations to increase older adult J Geriatr Oncol. 2016;7(5):346–353. https://doi.
46. Hamaker M, Lund C, Te Molder M, et al.
accrual to National Cancer Institute clinical trials. org/10.1016/j.jgo.2016.07.010
Geriatric assessment in the management of older
J Natl Cancer Inst Monogr. 2022;2022(60):135–141.
33. Miller MG, Kneuss TG, Patel JN, Parala- patients with cancer—a systematic review (up-
https://doi.org/10.1093/jncimonographs/lgac023
Metz AG, Haggstrom DE. Identifying potentially date). J Geriatr Oncol. 2022;13(6):761–777.
20. Celis ESPD, Li D, Sun C-L, et al. Patient- inappropriate medication (PIM) use in geriatric https://doi.org/10.1016/j.jgo.2022.04.008
defined goals and preferences among older adults oncology. J Geriatr Oncol. 2021;12(1):34–40.
47. Dale W, Williams GR, RM A, et al. How is
with cancer starting chemotherapy (CT). J Clin https://doi.org/10.1016/j.jgo.2020.06.013
geriatric assessment used in clinical practice for
Oncol. 2018;36(15_suppl):10009-10009. https://
34. Presley CJ, Dotan E, Soto-Perez-De-Celis E, older adults with cancer? A survey of cancer pro-
doi.org/10.1200/JCO.2018.36.15_suppl.10009
et al. Gaps in nutritional research among older viders by the American Society of Clinical
21. Paillaud E, Caillet P, Laurent M, et al. Optimal adults with cancer. J Geriatr Oncol. 2016;7(4):281– Oncology. JCO Oncol Pract. 2021;17(6):336–344.
management of elderly cancer patients: useful- 292. https://doi.org/10.1016/j.jgo.2016.04.006 https://doi.org/10.1200/OP.20.00442
ness of the Comprehensive Geriatric Assessment.
35. Meza-Valderrama D, Marco E, Dávalos- 48. Bellera CA, Rainfray M, Mathoulin-Pelissier S,
Clin Interv Aging. 2014;9:1645–1660. https://doi.
Yerovi V, et al. Sarcopenia, malnutrition, and et al. Screening older cancer patients: first evalu-
org/10.2147/cia.s57849
cachexia: adapting definitions and terminology of ation of the G-8 geriatric screening tool. Ann
22. Hurria A, Togawa K, Mohile SG, et al. Predict- nutritional disorders in older people with cancer. Oncol. 2012;23(8):2166–2172. https://doi.org/10.
ing chemotherapy toxicity in older adults with Nutrients. 2021;13(3):761. https://doi.org/10. 1093/annonc/mdr587
cancer: a prospective multicenter study. J Clin 3390/nu13030761
49. Extermann M, Boler I, Reich RR, et al. Pre-
Oncol. 2011;29(25):3457–3465. https://doi.org/
36. Mohile SG, Klepin HD, Rao AV. Considerations dicting the risk of chemotherapy toxicity in older
10.1200/JCO.2011.34.7625
and controversies in the management of older patients: the Chemotherapy Risk Assessment Scale
23. Verweij NM, Schiphorst AHW, Pronk A, Van patients with advanced cancer. Am Soc Clin Oncol for High-Age Patients (CRASH) score. Cancer.
Den Bos F, Hamaker ME. Physical performance Educ Book. 2012;(32):321–328. https://doi.org/10. 2012;118(13):3377–3386. https://doi.org/10.1002/
measures for predicting outcome in cancer pa- 14694/EdBook_AM.2012.32.168 cncr.26646
tients: a systematic review. Acta Oncol.
37. Bar-Sela G, Zalman D, Semenysty V, Ballan E. 50. Chaibi P, Magne N, Breton S, et al. Influence of
2016;55(12):1386–1391. https://doi.org/10.1080/
The effects of dosage-controlled cannabis cap- geriatric consultation with comprehensive geri-
0284186x.2016.1219047
sules on cancer-related cachexia and anorexia atric assessment on final therapeutic decision in
24. Dotan E, Walter LC, Beechinor R, et al. NCCN syndrome in advanced cancer patients: pilot study. elderly cancer patients. Crit Rev Oncol Hematol.
Guidelines insights: older adult oncology, Integr Cancer Ther. 2019;18:153473541988149. 2011;79(3):302–307. https://doi.org/10.1016/
version 1.2023. J Natl Compr Canc Netw. 2023. https://doi.org/10.1177/1534735419881498 j.critrevonc.2010.08.004
25. Dale W, Klepin HD, Williams GR, et al. Practical 38. Balducci L, Extermann M. Management of 51. Kalsi T, Babic-Illman G, Ross PJ, et al. The
assessment and management of vulnerabilities in cancer in the older person: a practical approach. impact of comprehensive geriatric assessment in-
older patients receiving systemic cancer therapy: Oncologist. 2000;5(3):224–237. https://doi.org/ terventions on tolerance to chemotherapy in older
ASCO guideline update. J Clin Oncol. 2023;41(26): 10.1634/theoncologist.5-3-224 people. Br J Cancer. 2015;112(9):1435–1444.
4293–4312. https://doi.org/10.1200/jco.23.00933 https://doi.org/10.1038/bjc.2015.120
39. Giacalone A, Quitadamo D, Zanet E,
26. Williams GR, Mackenzie A, Magnuson A, et al. Berretta M, Spina M, Tirelli U. Cancer-related fa- 52. Li D, Sun CL, Kim H, et al. Geriatric
Comorbidity in older adults with cancer. J Geriatr tigue in the elderly. Support Care Cancer. Assessment-Driven Intervention (GAIN) on
Oncol. 2016;7(4):249–257. https://doi.org/10. 2013;21(10):2899–2911. https://doi.org/10.1007/ chemotherapy-related toxic effects in older adults
1016/j.jgo.2015.12.002 s00520-013-1897-1 with cancer: a randomized clinical trial. JAMA


27. Kirkhus L, Jordhøy M, Saltyt e_ Benth J, et al. 40. Podsiadlo D, Richardson S. The timed “up & go”: Oncol. 2021;7(11):e214158. https://doi.org/10.
Comparing comorbidity scales: attending physi- a test of basic functional mobility for frail elderly 1001/jamaoncol.2021.4158
cian score versus the Cumulative Illness Rating persons. J Am Geriatr Soc. 1991;39(2):142–148. 53. Mohile SG, Mohamed MR, Xu H, et al. Evaluation
Scale for Geriatrics. J Geriatr Oncol. 2016;7(2):90– https://doi.org/10.1111/j.1532-5415.1991.tb01616.x of geriatric assessment and management on the toxic
98. https://doi.org/10.1016/j.jgo.2015.12.003 effects of cancer treatment (GAP70þ): a cluster-
41. Hurria A, Li D, Hansen K, et al. Distress in older
28. Lee L, Cheung WY, Atkinson E, patients with cancer. J Clin Oncol. 2009;27(26): randomised study. Lancet. 2021;398(10314):1894–
Krzyzanowska MK. Impact of comorbidity on 4346–4351. https://doi.org/10.1200/jco.2008. 1904. https://doi.org/10.1016/S0140-6736(21)
chemotherapy use and outcomes in solid tumors: a 19.9463 01789-X
systematic review. J Clin Oncol. 2011;29(1):106–
42. Canoui-Poitrine F, Reinald N, Laurent M, et al. 54. Mohile SG, Dale W, Somerfield MR, et al.
117. https://doi.org/10.1200/JCO.2010.31.3049
Geriatric assessment findings independently Practical assessment and management of vulner-
29. Canoui-Poitrine F, Segaux L, Benderra M-A, associated with clinical depression in 1092 older abilities in older patients receiving chemotherapy:
et al. The prognostic value of eight comorbidity patients with cancer: the ELCAPA cohort study. ASCO guideline for geriatric oncology. J Clin Oncol.
indices in older patients with cancer: the ELCAPA Psychooncology. 2016;25(1):104–111. https://doi. 2018;36(22):2326–2347. https://doi.org/10.1200/
cohort study. Cancers. 2022;14(9):2236. https:// org/10.1002/pon.3886 jco.2018.78.8687
doi.org/10.3390/cancers14092236
43. Mitchell AJ. Pooled results from 38 analyses of 55. Magnuson A, Sedrak MS, Gross CP, et al.
30. Magnuson A, Ahles T, Chen BT, Mandelblatt J, the accuracy of distress thermometer and other Development and validation of a risk tool for
Janelsins MC. Cognitive function in older adults ultra-short methods of detecting cancer-related predicting severe toxicity in older adults receiving
JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024 Ioffe et al 157
APRIL 2024:143–158 Balancing CV Concerns and Cancer Treatment in OAs

chemotherapy for early-stage breast cancer. J Clin cancer and compromised heart function: the 79. Cunningham D, Lang I, Marcuello E, et al.
Oncol. 2021;39(6):608–618. https://doi.org/10. SAFE-HEaRt study. Breast Cancer Res Treat. Bevacizumab plus capecitabine versus capecita-
1200/jco.20.02063 2019;175(3):595–603. https://doi.org/10.1007/ bine alone in elderly patients with previously un-
s10549-019-05191-2 treated metastatic colorectal cancer (AVEX): an
56. Ezaz G, Long JB, Gross CP, Chen J. Risk pre-
open-label, randomised phase 3 trial. Lancet
diction model for heart failure and cardiomyopa- 67. Lubberts S, Groot HJ, De Wit R, et al. Cardio-
Oncol. 2013;14(11):1077–1085. https://doi.org/10.
thy after adjuvant trastuzumab therapy for breast vascular disease in testicular cancer survivors:
1016/S1470-2045(13)70154-2
cancer. J Am Heart Assoc. 2014;3(1):e000472. identification of risk factors and impact on quality
https://doi.org/10.1161/jaha.113.000472 of life. J Clin Oncol. 2023;41(19):3512–3522. 80. Lonardi S, Rasola C, Lobefaro R, et al. Initial
57. Dumontier C, Uno H, Hshieh T, et al. Ran- https://doi.org/10.1200/jco.22.01016 panitumumab plus FOLFOX or 5-FU/LV in elderly
domized controlled trial of geriatric consultation patients with RAS and BRAF wild-type metastatic
68. Davidson KW, Barry MJ, Mangione CM, et al.
versus standard care in older adults with hema- colorectal cancer: the PANDA trial by GONO
Aspirin use to prevent cardiovascular disease.
tologic malignancies. Haematologica. 2021;107(5): foundation. J Clin Oncol. 2023;41(34):5263–5273.
JAMA. 2022;327(16):1577. https://doi.org/10.
1172–1180. https://doi.org/10.3324/haematol. 1001/jama.2022.4983 81. Antonio M, Saldaña J, Carmona-Bayonas A, et al.
2021.278802 Geriatric assessment predicts survival and
69. Sanft T, Day A, Ansbaugh S, et al. NCCN
58. Mohile SG, Epstein RM, Hurria A, et al. competing mortality in elderly patients with early
Guidelines insights: survivorship, version 1.2023.
Communication with older patients with cancer colorectal cancer: can it help in adjuvant therapy
J Natl Compr Canc Netw. 2023;21(8):792–803.
using geriatric assessment. JAMA Oncol. decision-making? Oncologist. 2017;22(8):934–943.
70. Blaes A, Manisty C, Barac A. How to follow, https://doi.org/10.1634/theoncologist.2016-0462
2020;6(2):196. https://doi.org/10.1001/jamaon-
manage and treat cardiac dysfunction in patients
col.2019.4728 82. Lund CM, Vistisen KK, Olsen AP, et al. The
with HER2þ breast cancer. J Am Coll Cardiol Car-
59. Ijaz N, Buta B, Xue Q-L, et al. Interventions for effect of geriatric intervention in frail older pa-
dioOnc. 2020;2(4):661–665. https://doi.org/10.
frailty among older adults with cardiovascular tients receiving chemotherapy for colorectal can-
1016/j.jaccao.2020.08.010
disease. J Am Coll Cardiol. 2022;79(5):482–503. cer: a randomised trial (GERICO). Br J Cancer.
https://doi.org/10.1016/j.jacc.2021.11.029 71. Goyal P, Kwak MJ, Al Malouf C, et al. Geriatric 2021;124(12):1949–1958. https://doi.org/10.
cardiology: coming of age. JACC Adv. 2022;1(3): 1038/s41416-021-01367-0
60. Curigliano G, Lenihan D, Fradley M, et al. 100070. https://doi.org/10.1016/j.jacadv.2022.
Management of cardiac disease in cancer patients 83. Advani PP, Ballman KV, Dockter TJ, et al.
100070
throughout oncological treatment: ESMO Long-term cardiac safety analysis of NCCTG
72. Budnitz DS, Lovegrove MC, Shehab N, N9831 (Alliance) adjuvant trastuzumab trial. J Clin
consensus recommendations. Ann Oncol.
Richards CL. Emergency hospitalizations for Oncol. 2016;34(6):581–587. https://doi.org/10.
2020;31(2):171–190. https://doi.org/10.1016/j.
adverse drug events in older Americans. N Engl J 1200/jco.2015.61.8413
annonc.2019.10.023
Med. 2011;365(21):2002–2012. https://doi.org/10.


61. Pudil R, Mueller C, Celutkiene_ J, et al. Role of 84. Swain SM, Miles D, Kim SB, et al. Pertuzumab,
1056/nejmsa1103053
serum biomarkers in cancer patients receiving trastuzumab, and docetaxel for HER2-positive
73. Unlu O, Levitan EB, Reshetnyak E, et al. Poly- metastatic breast cancer (CLEOPATRA): end-of-
cardiotoxic cancer therapies: a position statement
pharmacy in older adults hospitalized for heart fail- study results from a double-blind, randomised,
from the Cardio-Oncology Study Group of the
ure. Circ Heart Fail. 2020;13(11):e006977. https:// placebo-controlled, phase 3 study. Lancet Oncol.
Heart Failure Association and the Cardio-Oncology
doi.org/10.1161/circheartfailure.120.006977 2020;21(4):519–530. https://doi.org/10.1016/
Council of the European Society of Cardiology. Eur
J Heart Fail. 2020;22(11):1966–1983. https://doi. S1470-2045(19)30863-0
74. Sheppard JP, Burt J, Lown M, et al. Effect of
org/10.1002/ejhf.2017 antihypertensive medication reduction vs usual 85. Miles D, Baselga J, Amadori D, et al. Treat-


62. Celutkien e_ J, Pudil R, López-Fernández T, care on short-term blood pressure control in pa- ment of older patients with HER2-positive meta-
et al. Role of cardiovascular imaging in cancer tients with hypertension aged 80 years and older. static breast cancer with pertuzumab,
patients receiving cardiotoxic therapies: a position JAMA. 2020;323(20):2039. https://doi.org/10. trastuzumab, and docetaxel: subgroup analyses
statement on behalf of the Heart Failure Associa- 1001/jama.2020.4871 from a randomized, double-blind, placebo-
tion (HFA), the European Association of Cardio- controlled phase III trial (CLEOPATRA). Breast
75. Du XL, Xia R, Liu C-C, et al. Cardiac toxicity
vascular Imaging (EACVI) and the Cardio-Oncology Cancer Res Treat. 2013;142(1):89–99. https://doi.
associated with anthracycline-containing chemo-
Council of the European Society of Cardiology org/10.1007/s10549-013-2710-z
therapy in older women with breast cancer. Can-
(ESC). Eur J Heart Fail. 2020;22(9):1504–1524. cer. 2009;115(22):5296–5308. https://doi.org/10. 86. Barrios CH, Anton A, Delaloge S, et al. Safety
https://doi.org/10.1002/ejhf.1957 1002/cncr.24621 of trastuzumab emtansine (T-DM1) in 373 patients
63. Lyon AR, López-Fernández T, Couch LS, et al. 65 years or older with HER2-positive advanced
76. Gil-Gil MJ, Bellet M, Bergamino M, et al. Long-
2022 ESC guidelines on cardio-oncology devel- breast cancer: a subgroup analysis of the Kamilla
term cardiac safety and survival outcomes of
oped in collaboration with the European Hema- study. J Clin Oncol. 2015;33(15_suppl):603-603.
neoadjuvant pegylated liposomal doxorubicin in
tology Association (EHA), the European Society https://doi.org/10.1200/jco.2015.33.15_suppl.603
elderly patients or prone to cardiotoxicity and
for Therapeutic Radiology and Oncology (ESTRO) triple negative breast cancer. Final results of the 87. Cortés J, Kim S-B, Chung W-P, et al. Trastu-
and the International Cardio-Oncology Society (IC- multicentre phase II CAPRICE study. Front Oncol. zumab deruxtecan versus trastuzumab emtansine
OS). Eur Heart J. 2022;43(41):4229–4361. https:// 2021;11:645026. https://doi.org/10.3389/fonc. for breast cancer. N Engl J Med. 2022;386(12):
doi.org/10.1093/eurheartj/ehac244 2021.645026 1143–1154. https://doi.org/10.1056/nejmoa2115022
64. Neuendorff NR, Loh KP, Mims AS, et al. Anthra- 77. Coltelli L, Fontana A, Lucchesi S, et al. Cardiac 88. Modi S, Jacot W, Yamashita T, et al. Trastuzumab
cycline-related cardiotoxicity in older patients with safety of adjuvant non-pegylated liposomal deruxtecan in previously treated HER2-low advanced
acute myeloid leukemia: a Young SIOG review paper. doxorubicin combined with cyclophosphamide and breast cancer. N Engl J Med. 2022;387(1):9–20.
Blood Adv. 2020;4(4):762–775. https://doi.org/10. followed by paclitaxel in older breast cancer pa- https://doi.org/10.1056/nejmoa2203690
1182/bloodadvances.2019000955 tients. Breast. 2017;31:186–191. https://doi.org/
65. Guglin M, Krischer J, Tamura R, et al. Ran- 10.1016/j.breast.2016.11.006 89. Bair SM, Choueiri TK, Moslehi J. Cardiovascu-
domized trial of lisinopril versus carvedilol to pre- lar complications associated with novel angio-
78. Polk A, Vaage-Nilsen M, Vistisen K, et al. genesis inhibitors: emerging evidence and
vent trastuzumab cardiotoxicity in patients with
Cardiotoxicity in cancer patients treated with evolving perspectives. Trends Cardiovasc Med.
breast cancer. J Am Coll Cardiol. 2019;73(22):2859–
5-fluorouracil or capecitabine: a systematic re- 2013;23(4):104–113. https://doi.org/10.1016/
2868. https://doi.org/10.1016/j.jacc.2019.03.495
view of incidence, manifestations and predis- j.tcm.2012.09.008
66. Lynce F, Barac A, Geng X, et al. Prospective posing factors. Cancer Treat Rev. 2013;39(8):
evaluation of the cardiac safety of HER2-targeted 974–984. https://doi.org/10.1016/j.ctrv.2013. 90. Sclafani F, Cunningham D. Bevacizumab in
therapies in patients with HER2-positive breast 03.005 elderly patients with metastatic colorectal cancer.
158 Ioffe et al JACC: CARDIOONCOLOGY, VOL. 6, NO. 2, 2024

Balancing CV Concerns and Cancer Treatment in OAs APRIL 2024:143–158

J Geriatr Oncol. 2014;5(1):78–88. https://doi.org/ prostate cancer. N Engl J Med. 2019;380(13):1235– therapy for breast cancer. N Engl J Med.
10.1016/j.jgo.2013.08.006 1246. https://doi.org/10.1056/nejmoa1815671 2013;368(11):987–998. https://doi.org/10.1056/
94. Iacovelli R, Ciccarese C, Bria E, et al. The car- NEJMoa1209825
91. Amadio G, Marchetti C, Villani ER, et al. Toler-
diovascular toxicity of abiraterone and enzaluta- 97. Kunkler IH, Williams LJ, Jack WJL, et al.
ability of bevacizumab in elderly ovarian cancer
mide in prostate cancer. Clin Genitourin Cancer. Breast-conserving surgery with or without irradi-
patients (TURBO study): a case-control study of a
2018;16(3):e645–e653. https://doi.org/10.1016/ ation in early breast cancer. N Engl J Med.
real-life experience. J Gynecol Oncol. 2020;31(1):
j.clgc.2017.12.007 2023;388(7):585–594. https://doi.org/10.1056/
e6. https://doi.org/10.3802/jgo.2020.31.e6
95. Khosrow-Khavar F, Filion KB, Bouganim N, NEJMoa2207586
92. Chi KN, Agarwal N, Bjartell A, et al. Apaluta-
Suissa S, Azoulay L. Aromatase inhibitors and the
mide for metastatic, castration-sensitive prostate
risk of cardiovascular outcomes in women with
cancer. N Engl J Med. 2019;381(1):13–24. https://
breast cancer. Circulation. 2020;141(7):549–559. KEY WORDS aging, cancer, cardio-
doi.org/10.1056/nejmoa1903307
https://doi.org/10.1161/circulationaha.119.044750 oncology, cardiovascular disease, geriatric
93. Fizazi K, Shore N, Tammela TL, et al. Dar- 96. Darby SC, Ewertz M, McGale P, et al. Risk of assessment, geriatric domains, geriatric
olutamide in nonmetastatic, castration-resistant ischemic heart disease in women after radio- oncology